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April 12, 2016; 86 (15) Article

Age at onset and Parkinson disease phenotype

Gennaro Pagano, Nicola Ferrara, David J. Brooks, Nicola Pavese
First published February 10, 2016, DOI: https://doi.org/10.1212/WNL.0000000000002461
Gennaro Pagano
From the Department of Medicine (G.P., D.J.B., N.P.), Neurology Imaging Unit, Imperial College London, Hammersmith Hospital, London, UK; Department of Translational Medical Sciences (G.P., N.F.), Federico II University of Naples; Salvatore Maugeri Foundation (N.F.), IRCCS, Scientific Institute of Telese, Telese Terme (BN), Italy; and Department of Clinical Medicine–Center for Functionally Integrative Neuroscience (D.J.B., N.P.), Aarhus University, Denmark.
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Nicola Ferrara
From the Department of Medicine (G.P., D.J.B., N.P.), Neurology Imaging Unit, Imperial College London, Hammersmith Hospital, London, UK; Department of Translational Medical Sciences (G.P., N.F.), Federico II University of Naples; Salvatore Maugeri Foundation (N.F.), IRCCS, Scientific Institute of Telese, Telese Terme (BN), Italy; and Department of Clinical Medicine–Center for Functionally Integrative Neuroscience (D.J.B., N.P.), Aarhus University, Denmark.
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David J. Brooks
From the Department of Medicine (G.P., D.J.B., N.P.), Neurology Imaging Unit, Imperial College London, Hammersmith Hospital, London, UK; Department of Translational Medical Sciences (G.P., N.F.), Federico II University of Naples; Salvatore Maugeri Foundation (N.F.), IRCCS, Scientific Institute of Telese, Telese Terme (BN), Italy; and Department of Clinical Medicine–Center for Functionally Integrative Neuroscience (D.J.B., N.P.), Aarhus University, Denmark.
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Nicola Pavese
From the Department of Medicine (G.P., D.J.B., N.P.), Neurology Imaging Unit, Imperial College London, Hammersmith Hospital, London, UK; Department of Translational Medical Sciences (G.P., N.F.), Federico II University of Naples; Salvatore Maugeri Foundation (N.F.), IRCCS, Scientific Institute of Telese, Telese Terme (BN), Italy; and Department of Clinical Medicine–Center for Functionally Integrative Neuroscience (D.J.B., N.P.), Aarhus University, Denmark.
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Citation
Age at onset and Parkinson disease phenotype
Gennaro Pagano, Nicola Ferrara, David J. Brooks, Nicola Pavese
Neurology Apr 2016, 86 (15) 1400-1407; DOI: 10.1212/WNL.0000000000002461

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Abstract

Objective: To explore clinical phenotype and characteristics of Parkinson disease (PD) at different ages at onset in recently diagnosed patients with untreated PD.

Methods: We have analyzed baseline data from the Parkinson's Progression Markers Initiative database. Four hundred twenty-two patients with a diagnosis of PD confirmed by DaTSCAN imaging were divided into 4 groups according to age at onset (onset younger than 50 years, 50–59 years, 60–69 years, and 70 years or older) and investigated for differences in side, type and localization of symptoms, occurrence/severity of motor and nonmotor features, nigrostriatal function, and CSF biomarkers.

Results: Older age at onset was associated with a more severe motor and nonmotor phenotype, a greater dopaminergic dysfunction on DaTSCAN, and reduction of CSF α-synuclein and total tau. The most common presentation was the combination of 2 or 3 motor symptoms (bradykinesia, resting tremor, and rigidity) with rigidity being more common in the young-onset group. In about 80% of the patients with localized onset, the arm was the most affected part of the body, with no difference across subgroups.

Conclusions: Although the presentation of PD symptoms is similar across age subgroups, the severity of motor and nonmotor features, the impairment of striatal binding, and the levels of CSF biomarkers increase with age at onset. The variability of imaging and nonimaging biomarkers in patients with PD at different ages could hamper the results of future clinical trials.

GLOSSARY

Aβ1–42=
β-amyloid 1–42;
α-syn=
α-synuclein;
HC=
healthy control;
HVLT=
Hopkins Verbal Learning Test;
H&Y=
Hoehn and Yahr;
MDS-UPDRS=
Movement Disorder Society–Unified Parkinson's Disease Rating Scale;
MoCA=
Montreal Cognitive Assessment;
PD=
Parkinson disease;
PPMI=
Parkinson's Progression Markers Initiative;
p-tau181=
tau phosphorylated at Thr181;
SCOPA-AUT=
Scales for Outcomes in Parkinson's Disease–Autonomic;
STAI=
State-Trait Anxiety Inventory;
t-tau=
total tau;
UPSIT=
University of Pennsylvania Smell Identification Test

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received August 9, 2015.
  • Accepted in final form November 25, 2015.
  • © 2016 American Academy of Neurology
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